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Abstract
Early investigational trials with new quinolone antibiotics revealed two important
drug-drug interactions: decreased fluoroquinolone absorption when co-administered
with magnesium-aluminum antacids and inhibition of theophylline metabolism. Subsequent
studies have investigated the mechanisms of these interactions. With respect to the
effect of antacids, the absorption of all quinolones appears to be significantly reduced
by antacids containing magnesium and/or aluminum, and concomitant administration must
be avoided. Other cations, such as calcium, iron, and probably zinc, appear to interact
in a similar manner. Chelation between the quinolone and cation is the most likely
mechanism. With respect to the effect on the theophylline metabolism, quinolones inhibit
specific cytochrome P-450 isozymes responsible for metabolism of methylxanthines,
although there are major differences between the quinolones. Enoxacin is the most
potent inhibitor, followed by ciprofloxacin, pefloxacin, norfloxacin, and ofloxacin.
Caffeine metabolism is also inhibited, although the clinical significance is uncertain.
Case reports describe renal failure associated with concomitant administration of
cyclosporine and ciprofloxacin, although controlled trials have not demonstrated an
interaction. Enoxacin has little effect on warfarin metabolism, suggesting that other
quinolones may not affect warfarin disposition. Case reports of central nervous system
toxicity from administration of nonsteroidal anti-inflammatory agents and quinolones
need confirmation. Patients should be monitored closely when potential interacting
agents are used; it is probable that not all interactions have been identified.
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© 1989 Published by Elsevier Inc.
